Sodium t-butoxide → 4-[4-Methyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-4-ylamino)-phenylsulfanyl]-phenol

HRID 607156ノート

反応式

HRID 607156 の反応式
Cl[C:2]1[C:3]2[C:4](=[N:8][N:9]([CH3:11])[CH:10]=2)[N:5]=[CH:6][CH:7]=1.[NH2:12][C:13]1[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:14]=1[S:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:19][C:17]1[CH:16]=[CH:15][C:14]([S:20][C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=2)=[C:13]([NH:12][C:2]2[C:3]3[C:4](=[N:8][N:9]([CH3:11])[CH:10]=3)[N:5]=[CH:6][CH:7]=2)[CH:18]=1

参加物

6

反応物 3

HCID 23676156Sodium t-butoxideHCID 668081234-(2-Amino-4-methyl-phenylsulfanyl)-phenolHCID 668084904-Chloro-2-methyl-2H-pyrazolo[3,4-b]pyridine

生成物 1

HCID 250106674-[4-Methyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-4-ylamino)-phenylsulfanyl]-phenol収率 21%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒2 回HCID 1140Toluene溶媒

実験手順

A mixture of the product of Example 8c (62.1 mg, 0.371 mmol), the product of Example 6c (85.7 mg, 0.371 mmol), Pd2(dba)3 (16.9 mg, 0.0185 mmol), sodium t-butoxide (89.0 mg, 0.926 mmol), and 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicycl[3,3,3]undecane (25.4 mg, 0.0741 mmol) in toluene (3 mL) was degassed, left under a positive pressure of nitrogen, and heated under reflux for 2 h. Additional amounts of Pd2(dba)3 (7.0 mg, 0.0076 mmol) and 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicycl[3,3,3]undecane (15 mg, 0.044 mmol) were added the reaction mixture was heated under reflux for an addition 2 h. The mixture was then cooled to room temperature and partitioned between ethyl acetate (30 mL) and water (30 mL). The aqueous phase was extracted with ethyl acetate and the combined organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, eluting with a 2-5% MeOH/CH2Cl2, gradient to provide the title compound (0.0279 g, 21% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm: 2.27 (s, 3H), 4.11 (s, 3H), 5.92 (d, J=5.15 Hz, 1H), 6.75-6.85 (m, 3H), 7.02 (dd, J=8.27, 0.92 Hz, 1H), 7.14 (s, 1H), 7.18-7.27 (m, 2H), 8.09 (d, J=5.15 Hz, 1H), 8.20 (s, 1H), 8.77 (s, 1H), 9.82 (s, 1H); MS (ESI+) m/z 363.0 (M+H)+ (ESI−) m/z 360.9 (M−H)−.

後処理

  1. waitleft under a positive pressure of nitrogen
  2. temperatureheated
  3. temperatureunder reflux for 2 h
  4. temperaturewas heated
  5. temperatureunder reflux for an addition 2 h
  6. custompartitioned between ethyl acetate (30 mL) and water (30 mL)
  7. extractionThe aqueous phase was extracted with ethyl acetate
  8. washthe combined organic phase was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customThe residue was purified by chromatography on silica gel
  13. washeluting with a 2-5% MeOH/CH2Cl2, gradient

出典と根拠

ORDレコード
ord-a543db252a8944a28187912b636f3db4
出典データセット
uspto-grants-2011_03
特許番号
US07915411B2

反応ノート

読み込み中…